CircPTEN-MT from <i>PTEN</i> regulates mitochondrial energy metabolism

Danhui Ruan; Jiancheng Xu; Yang Liu; Juan Luo; Xuyang Zhao; Yuhua Li; Guangxi Wang; Jiawen Feng; Hui Liang; Yue Yin; Jianyuan Luo; Yuxin Yin

doi:10.1016/j.jgg.2023.12.011

Volume 51 Issue 5

May 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(5): 531-542

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CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

doi: 10.1016/j.jgg.2023.12.011

a. Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University International Cancer Institute, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China;
b. Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China;
c. Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
d. Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

Funds:

We thank Q. Yin for technical assistance and critical discussions. This study is supported by grants to Y. Yin including the National Natural Science Foundation of China (82030081 and 81874235), the National Key Research and Development Program of China (2021YFA1300601), and the Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project (JCYJ20220818102811024). Y. Yin is the Scholar of the Lam Chung Nin Foundation for Systems Biomedicine. J. Xu was supported by the Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences.

Received Date: 2023-08-28
Accepted Date: 2023-12-28
Rev Recd Date: 2023-12-27

Available Online: 2025-06-06

Publish Date: 2024-01-05

Abstract

Abstract

Phosphatase and tensin homolog (PTEN) is a multifunctional gene involved in a variety of physiological and pathological processes. Circular RNAs (circRNAs) are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins. However, PTEN-related circRNAs are largely unknown. Here, we report that circPTEN- mitochondria (MT) (hsa_circ_0002934) is a circular RNA encoded by exons 3, 4, and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism. CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), which regulates posttranscriptional gene expression in mitochondria. Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator (SRA) stem-loop interacting RNA binding protein (SLIRP) and inhibits the polyadenylation of mitochondrial mRNA, which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production. Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism. This study expands our understanding of the role of PTEN, which produces both linear and circular RNAs with different and independent functions.
- Circular RNA,
- LRPPRC,
- Mitochondrial energy metabolism,
- mtDNA post-transcriptional regulation

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References(52)

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